The leading academic journal Nature today launched three papers simultaneously, offering new perspectives on improving the effectiveness of cancer immunotherapy. Three independent studies from the French National Institute of Health and Medical Research (INSERM), the University of Texas’ Anderson Cancer Center and Lund University in Sweden have given the immune system a key role in the B-cells, standing in the spotlight against tumors.
Today’s nature review of the three studies (Image Source: Resources)
When it comes to immunotherapy, many readers may not be unfamiliar. This innovative cancer treatment, which mobilizes the patient’s own immune system to fight tumours, has miraculously escaped death for many cancer patients who were previously drug-free.
Unfortunately, however, immunotherapy is not a panacea. Only about 20 per cent of current immunotherapy patients have long-term clinical benefits. Why do some patients have better results? If you can figure out how this works, it could help develop new therapies that benefit more patients.
Existing immunotherapy mainly focuses on killer T-cells in the immune system, improving their ability to identify and attack cancer cells. The three papers also point out that T-cells are not the only immune cells capable of fighting cancer.
B cells produce immune effects mainly through the secretion of antibodies (Photo: 123RF)
In patients with multiple different types of cancer, the three studies observed that patients received better immunotherapy when B cells formed a cell cluster within the tumor called tertiary lymphatic structures (orrony lymphoid structures, TLS).
“You can think of the function of the tertiary lymphatic structure as a ‘school’ for immune cells, helping them to educate them and effectively learn how to identify and attack cancer cells. Wolf Fridman, a leading Professor of Immunology in France and the head of one of the studies, explains vividly.
Professor Fridman’s team analyzed the gene expression spectrum of more than 600 soft tissue sarcoma, dividing the sample into subgroups based on the characteristics of immune cells. They found that B-cells were the strongest prognostic factor, and that the immune subgroup, rich in B cells, had the highest survival rates after being treated with anti-PD1 monoantigens during clinical trials.
The second study studied the effects of B-cells in clinical samples of metastatic melanoma, and found that CD8-positive T-cells and CD20-positive B cells appeared simultaneously, predicting higher survival rates in patients. Analysis of molecular phenotypes showed that tertiary lymphatic structures played a key role in the immune microenvironment of melanoma, giving T-cells different phenotypes.
The third study began with a comparison of tumors that were effective and ineffective against immunotherapy in melanoma patients. The results of large-scale RNA sequencing show that B-cell markers are the most obvious gene in two types of tumors that express differences. The team then tested kidney cell cancer patients and melanoma patients treated with immunocheckpoint inhibitors in both groups.
“We found that B cells are not idle bystanders, but also make a meaningful contribution to the immune response to tumors. “The study’s lead author, Dr. Beth Helmink of the University of Texas Anderson Cancer Center, said.
B cells are a class of immune cells that produce antibodies. While it’s not clear exactly how B cells in the tertiary lymphatic structure work, scientists speculate that B cells on the front line of anti-tumor may produce antibodies to fight cancer cells effectively, or they may work by supporting T-cells.
B cells in the microenvironment of the tumor can also play a role in fighting the tumor (Photo: Supplied)
Nature magazine highly rated the discovery, specifically published an exclusive review. In his review, immunologist Professor Tullia Bruno noted that the paper “has insight and uses statistically reliable clinical data to bring B-cells and tertiary lymphocytes to the forefront of anti-tumor immunity”. These results also point to new directions for follow-up studies, combining T-cell-mediated immunotherapy with the use of B-cells, which promises to have effective anti-cancer effects in more patients.